Chitosan is known as a chitin derivative obtained by partial to substantial alkaline N-deacetylation of chitin also named poly(N-acetyl-D-glucosamine), which is a naturally occurring biopolymer.
Chitosan contains free amine (—NH2) groups and acetyl groups and may be characterized as to the proportion of N-acetyl-D-glucosamine units and D-glucosamine units, and such is expressed as the degree of deacetylation (DD) of the fully acetylated polymer chitin.
Parameters of chitosan influencing important properties such as solubility and viscosity are the degree of deacetylation (DD) which may be understood as representing the percentage of deacetylated monomers, and the average molecular weight (MW). Chitosan is known to be biodegradable, biocompatible, bioadhesive, bacteriostatic, and further to be able to promote wound-healing, drug absorption, and tissue reconstruction. Due to its above mentioned intrinsic properties, chitosan has found numerous cosmetic and pharmaceutical applications, for instance ophthalmic applications, in regenerative medicine, or for wound healing.
Therefore, considering the advantageous properties of chitosan and its numerous applications, there have been many attempts to produce sterile and stable compositions comprising chitosan.
WO 97/007139 discloses a process for sterilizing a polysaccharide composition containing water-insoluble chitosan without substantially degrading the polysaccharide. In this process, water-insoluble chitosan is first dispersed in water, then sterilized under high pressure steam to form a chitosan suspension with a pH equal to or higher than about 7. The suspended chitosan particles of said suspension are finally dissolved in an aseptic acid to decrease the final pH and form a sterilized chitosan solution.
Jarry et al. 2002, Chem. Pharm. Bull., 50(10): 1335-1340 disclose a composition containing a chitosan free base dissolved in HCl and glycerol, having a final pH of about 5.25 after autoclaving. Addition of glycerophosphate to this solution increases the pH to about 7.14 and produces a turbid solution (presence of precipitates).
Despite the development of sterile compositions comprising chitosan, there is a continuous need to further improve the properties of known chitosan compositions, in particular to provide aqueous formulations containing chitosan having a pH close to the neutral pH, which are stable, clear, and viscous after heat sterilization and which are suitable for pharmaceutical use.